Serum inflammatory cytokines as disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy.

Autor:	Riddell DO; Comparative Neuromuscular Diseases Laboratory, Department of Clinical Science and Services, Royal Veterinary College, Camden, London NW1 0TU, UK., Hildyard JCW; Comparative Neuromuscular Diseases Laboratory, Department of Clinical Science and Services, Royal Veterinary College, Camden, London NW1 0TU, UK., Harron RCM; Comparative Neuromuscular Diseases Laboratory, Department of Clinical Science and Services, Royal Veterinary College, Camden, London NW1 0TU, UK., Hornby NL; Comparative Neuromuscular Diseases Laboratory, Department of Clinical Science and Services, Royal Veterinary College, Camden, London NW1 0TU, UK., Wells DJ; Department of Comparative Biomedical Sciences, Royal Veterinary College, Camden, London NW1 0TU, UK., Piercy RJ; Comparative Neuromuscular Diseases Laboratory, Department of Clinical Science and Services, Royal Veterinary College, Camden, London NW1 0TU, UK.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2022 Dec 01; Vol. 15 (12). Date of Electronic Publication: 2022 Dec 09.
DOI:	10.1242/dmm.049394
Abstrakt:	Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease, caused by mutations in the dystrophin gene, characterised by cycles of muscle degeneration, inflammation and regeneration. Recently, there has been renewed interest specifically in drugs that ameliorate muscle inflammation in DMD patients. The DE50-MD dog is a model of DMD that closely mimics the human DMD phenotype. We quantified inflammatory proteins in serum from wild-type (WT) and DE50-MD dogs aged 3-18 months to identify biomarkers for future pre-clinical trials. Significantly higher concentrations of C-C motif chemokine ligand 2 (CCL2), granulocyte-macrophage colony-stimulating factor (GM-CSF or CSF2), keratinocyte chemotactic-like (KC-like, homologous to mouse CXCL1), TNFα (or TNF), and interleukins IL2, IL6, IL7, IL8 (CXCL8), IL10, IL15 and IL18 were detected in DE50-MD serum compared to WT serum. Of these, CCL2 best differentiated the two genotypes. The relative level of CCL2 mRNA was greater in the vastus lateralis muscle of DE50-MD dogs than in that of WT dogs, and CCL2 was expressed both within and at the periphery of damaged myofibres. Serum CCL2 concentration was significantly associated with acid phosphatase staining in vastus lateralis biopsy samples in DE50-MD dogs. In conclusion, the serum cytokine profile suggests that inflammation is a feature of the DE50-MD phenotype. Quantification of serum CCL2 in particular is a useful non-invasive biomarker of the DE50-MD phenotype. Competing Interests: Competing interests R.J.P. has received funding for separate research programmes from Pfizer and Exonics Therapeutics and has been a consultant to Exonics Therapeutics; the financial interests were reviewed and approved by the Royal Veterinary College in accordance with conflict-of-interest policies. D.J.W. is or has been a consultant to a wide range of companies with interests in the DMD space, including Pfizer, Sarepta, Akashi and Actual Analytics. Studies in his lab have been funded by Proximagen and Shire. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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